The acquired immunodeficiency syndrome (AIDS) epidemic affected more than 100,000 United States citizens over the last ten years and has accounted for more than 68,000 deaths in this population. It is projected that by 1994, 200,000 more United States citizens will die from AIDS. The causative agent for AIDS is the human immunodeficiency virus (HIV-1) that was identified by immunocytochemistry in skin macrophages (Langerhan's cells). The isolation of HIV-1 was the first step in continuing attempts to produce an effective anti-HIV-1 vaccine. The precise incubation period from HIV-1 infection to disease development is unknown and may vary between individuals, but epidemiological studies and statistical modeling of current information suggest that the incubation period varies from 215 years. Acquired immunodeficiency syndrome is characterized by the profound loss of ability to respond to environmental antigens as well as the development of Kaposi's sarcoma. These studies are designed to investigate the immunology of AIDS and AIDS-related diseases. HIV-1, the causative agent for AIDS, specifically depletes a subpopulation of human T-lymphocytes that bear the CD4 cell surface marker. This molecule functions to stabilize MHC class II interactions. Thus, it was reasoned that the specific receptor for HIV-1 (CD4) might also involve products of the human major histocompatibility complex (MHC) genes. Studies undertaken include investigation of T-lymphocyte depletion in HIV-1 seropositive individuals and examination of the nature of receptor site for virus attachment as well as the mechanism of T4 lymphocyte (helper cell) destruction. These studies are also directed towards an understanding of the immune responses to these viruses and identification of possible genetic factors that affect disease susceptibility and progression in HIV-1 seropositive individuals.